The Cell Growth and Survival (CGS) program is composed of 20 members whose research involves basic studies related to the regulation of growth and death of tumor cells. An additional component of these research project is an effort to translate these basic findings in growth and death regulation into targeted therapeutic strategies that can be used to treat human cancer. The fosters collaborative interactions within the CGS program, as well as collaborative efforts with members of other programs within the CCCWFU. The mechanisms utilized for this effort include: 1) regular programmatic meetings and seminars, 2) yearly review of individual research projects through an annual retreat and an individual review with the Program Director, 3) the use of pilot funds to encourage innovative new research approaches, 4) the development of shared resources that enhance the potential methods available for research, and 5) direct involvement by the Program Director in recruitment of new faculty with cancer-focused research. The current membership has $2.436 in direct costs in cancer-focused grants, with $1.04 million derived from NCI. The Specific Aims of the CGS program for the next five years include the promotion of research focused on the following topics: 1) To define the differences in the mechanisms of growth and death regulation between normal and neoplastic cells. This aim includes projects that involve studies of the vitamin D receptor response pathway, alterations in gene expression in breast cancer, the tumor-resistant phenotype of a new strain of S180-resistant mice, the regulation of apoptotic threshold in response to toxins, and alterations in tumor suppressor genes in neoplasia. 2) To clarify the biological basis and therapeutic potential of targeted agents directed towards cancer cells. This aim includes projects involving development of fusion toxins for targeted therapy, the study of RXR, PPARgamma and the vitamin D receptor pathways for selective inhibition of tumor cell growth, and the design of antisense dendrimers for targeted therapy of neoplasia.